Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study.
Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study.
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DOI：
10.1200/jco.2016.67.4887
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发表时间：
2017-01-10
期刊：
影响因子：
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通讯作者：
Ellis P
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作者：
Perez EA;Barrios C;Eiermann W;Toi M;Im YH;Conte P;Martin M;Pienkowski T;Pivot X;Burris H 3rd;Petersen JA;Stanzel S;Strasak A;Patre M;Ellis P
曲妥珠单抗和帕妥珠单抗是人表皮生长因子受体2（HER 2）靶向单克隆抗体，曲妥珠单抗-美坦新偶联物（T-DM 1）是一种抗体-药物偶联物，结合了曲妥珠单抗的特性和DM 1的细胞毒性活性。T-DM 1在既往未经治疗的HER 2阳性转移性乳腺癌患者的II期研究中显示出令人鼓舞的疗效和安全性。T-DM 1和帕妥珠单抗组合在细胞培养模型中显示出协同活性，并且在Ib期和II期研究中具有可接受的安全性特征。在MARIANNE研究中，1,095例中心评估的HER 2阳性晚期乳腺癌患者和既往未接受过晚期疾病治疗的患者以1：1：1的比例随机分配至对照组（曲妥珠单抗+紫杉烷）、T-DM 1+安慰剂组（以下简称T-DM 1）或T-DM 1+帕妥珠单抗组（标准剂量）。主要终点是无进展生存期（PFS），由独立审查评估。T-DM 1和T-DM 1+帕妥珠单抗显示PFS非劣效于曲妥珠单抗+紫杉烷（中位PFS：曲妥珠单抗+紫杉烷组为13.7个月，T-DM 1组为14.1个月，T-DM 1+帕妥珠单抗组为15.2个月）。两个实验组均未显示PFS优于曲妥珠单抗+紫杉烷。曲妥珠单抗+紫杉烷治疗患者的缓解率为67.9%，T-DM 1为59.7%，T-DM 1+帕妥珠单抗为64.2%;中位缓解持续时间分别为12.5个月、20.7个月和21.2个月。对照组（54.1%）中≥ 3级不良事件的发生率在数值上高于T-DM 1组（45.4%）和T-DM 1+帕妥珠单抗组（46.2%）。T-DM 1组中因不良事件而停止治疗的患者数量较少，T-DM 1组中健康相关生活质量维持时间更长。T-DM 1在HER 2阳性晚期乳腺癌的一线治疗中显示出非劣效但非上级的疗效和更好的耐受性。
Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) –targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody–drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast cancer.